In the men's 100m butterfly final Olympic champion Chad le Clos set a new championship record of 48.82 seconds to claim gold and deny American Ryan Lochte another title.
Lochte had looked comfortable in winning the 200m freestyle on the opening night, but had to make do with third on Thursday 0.05 seconds behind teammate Thomas Shields and 0.77 behind South African le Clos.
Meilutyte produced one of the upsets of the London 2012 Olympics when she beat American four-time world champion Rebecca Soni to gold in the 100m breaststroke aged just 15.
And she ensured that was far from a fluke with another impressive victory at the World Short Course Championships in Istanbul, this time over half the distance in the 50m breaststroke.
The 15-year-old set a new European record on the way to Olympic gold and her performance in Turkey was record breaking again as she lowered the championship record to 29.44 seconds.
Meilutyte, who studies at Plymouth College but swims for her country of birth Lithuania, was 0.23 ahead of Alia Atkinson who took silver while Sarah Katsoulis was 0.50 behind for bronze.
However Britain did not have anything to cheer outright on the second night as Georgia Davies set a new Welsh record in the 100m backstroke final but was two places off the podium positions.
Davies clocked 57.32 as American Olivia Smoliga took gold in 56.64 with another impressive teenager, 16-year-old Mie Oestergaard Nielsen, second and Simona Baumrtova third.
Meanwhile Hannah Miley, who won the 400m medley title on the first night, narrowly missed out on claiming a second medal in the 800m freestyle as she finished an agonising fourth.
Miley was just over half a second shy of bronze medallist Chloe Sutton after clocking 8:16.09minutes as Lauren Boyle of New Zealand took gold ahead of two-time world champion Lotte Friis in 8:08.62.
Eleanor Faulkner was ranked eighth after posting 8:22.96 while the British men's 4x200m freestyle relay quartet of Ieuan Lloyd, Chris Walker-Hebborn, Roberto Pavoni and Robbie Renwick finished seventh.
Lloyd lowered his Welsh record again to 1:45.24 on the first leg as Britain clocked 7:05.73 with America taking gold in 6:51.40 ahead of the quartets from Australia and Germany.
Britain are guaranteed a shot at a medal on the third night of action in Istanbul though with Sophie Allen qualifying out of the 100m medley semi-finals as the sixth fastest in 59.58.
Elsewhere Japan's Daiya Seto was the only swimmer to break the four-minute barrier in the 400m medley as he beat off competition from European short course champion Laszlo Cseh to win gold.
Seto clocked 3:59.15 in the final, 1.35 quicker than Cseh who was in turn over two seconds quicker than bronze medallist and Hungarian teammate David Verraszto.
And in the men's 100m backstroke final Matthew Grevers beat Russia's Stanislav Donets to gold at the touch, the American's winning margin in Istanbul just 0.02.
Guilherme Guido was over half a second behind in third while Italian Fabio Scozzoli added the world short course 100m breaststroke title to the European crown he claimed last month.
Men's 400m Individual Medley Final
1.Daiya Seto (Japan) 3:59.15 2. Laszlo Cseh (Hungary) 4:00.50 3. David Verraszto (Hungary) 4:02.87
Women's 50m Breaststroke Final
1.Ruta Meilutyte (Lithuania) 29.44 2. Alia Atkinson (Jamaica) 29.67 3. Sarah Katsoulis (Australia) 29.94
Men's 100m Backstroke Final
1. Matthew Grevers (U.S.) 49.89 2. Stanislav Donets (Russia) 49.91 3. Guilherme Guido (Brazil) 50.50
Women's 100m Backstroke Final
1. Olivia Smoliga (U.S.) 56.64 2. Mie Nielsen (Denmark) 57.07 3. Simona Baumrtova (Czech Republic) 57.18
Men's 100m Breaststroke Final
1. Fabio Scozzoli (Italy) 57.10 2. Damir Dugonjic (Slovenia) 57.32 3. Kevin Cordes (U.S.) 57.83
Men's 100m Butterfly Final
1. Chad Le Clos (South Africa) 48.82 2. Tom Shields (U.S.) 49.54 3. Ryan Lochte (U.S.) 49.59
Women's 800m Freestyle
1. Lauren Boyle (New Zealand) 8:08.62 2. Lotte Friis (Denmark) 8:10.99 3. Chloe Sutton (U.S.) 8:15.53
Men's 4 x 200m Freestyle Relay Final
1.USA R.Lochte/C.Dwyer/M.Klueh/M.McLean 6:51.40 2. Australia T.D'Orsogna/J.Killey/K.Richardson/R.Hurley 6:52.29 3. Germany P.Biedermann/D.Colupaev/C.Fildebrandt/Y.Lebherz 6:53.22